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Titolo:
Sialyltransferase inhibitors based on CMP-quinic acid
Autore:
Schaub, C; Muller, B; Schmidt, RR;
Indirizzi:
Univ Konstanz, Fak Chem, D-78457 Constance, Germany Univ Konstanz Constance Germany D-78457 Chem, D-78457 Constance, Germany
Titolo Testata:
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
fascicolo: 9, , anno: 2000,
pagine: 1745 - 1758
SICI:
1434-193X(200005):9<1745:SIBOCA>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
TRANSITION-STATE ANALOGS; SIALYL-LEWIS-X; CMP-NEU5AC; ESTERS; CONFIGURATION; ACTIVATION; ALCOHOLS; DONOR;
Keywords:
CMP-Neu5Ac analogues; enzyme inhibitors; substrate analogues; transition state analogues; (2-6)-sialyltransferase; carbohydrates;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Physical, Chemical & Earth Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Schmidt, RR Univ Konstanz, Fak Chem, Fach M 725, D-78457 Constance, Germany Univ Konstanz Fach M 725 Constance Germany D-78457 e, Germany
Citazione:
C. Schaub et al., "Sialyltransferase inhibitors based on CMP-quinic acid", EUR J ORG C, (9), 2000, pp. 1745-1758

Abstract

Quinic acid was transformed into phosphitamides 16, 25, and 36, which could be readily linked to 5'-O-unprotected cytidine derivative 17. Ensuing oxidation of the obtained phosphite triesters with tBuO(2)H and hydrogenolyticde-O-benzylation furnished the corresponding phosphate diesters 18, 26, and 38, Base catalyzed removal of acetyl protecting groups, and methyl ester hydrolysis furnished CMP-Neu5Ac analogues Id, le, and 2, Quinic acid was also transformed into 1,2-unsaturated diallyl alpha-hydroxymethyl-phosphate derivatives (R)- and (S)-46,which on reaction with cytidine phosphitamide 47afforded the phosphite triesters. Subsequent oxidation with tBuO(2)H and then treatment with NEt3 gave phosphate diester derivatives (R)- and (S)-48. Deallylation, acetyl group removal, and methyl ester hydrolysis furnished (R)- and (S)-3, respectively. Treatment of (R)- and (S)-48 with DBU as a base led to acetic acid elimination, thus yielding, after de-O-allylation, acetyl group cleavage, and ester hydrolysis, diene derivative (E)-4. Donor substrate analogues Id and 1e exhibited good alpha(2-6)-sialyltransferase inhibition (K-i: 2.0.10(-4) and 2.0.10(-5) M). However, transition state analogues (R)-, and particularly (S)-3 showed excellent inhibition properties (K-i,: 1.6.10(-6) and 2.7.10(-7) M).

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Documento generato il 02/04/20 alle ore 09:19:56